The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation.

Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.

Kaposi's sarcoma-associated herpesvirus lana2 protein interacts with the pocket proteins and inhibits their sumoylation.

The pocket proteins retinoblastoma protein (pRb), p107 and p130 are the key targets of oncoproteins expressed by DNA tumor viruses. Some of these viral proteins contain an LXCXE motif that mediates the interaction with the three pocket proteins and the inhibition of the pRb SUMOylation. Kaposi's sarcoma herpesvirus (KSHV) contains at least two proteins that can regulate pRb function but, so far, a KSHV-encoded protein targeting p107 and p130 has not been identified. Here, we show that the KSHV latent protein LANA2 binds to pRb, p107 and p130. LANA2 contains an LXCXE motif that is required for bypassing pRb-mediated cell-cycle arrest and for inhibiting pRb SUMOylation. Finally, we demonstrate that, in addition to pRb, both p107 and p130 can be SUMOylated, and this modification is also inhibited by LANA2 in an LXCXE-dependent manner. These results demonstrate, for the first time, the SUMOylation of p107 or p130 and, so far, they represent the first example of a KSHV protein able to interact with the three pocket proteins and to inhibit their conjugation to SUMO.

Regulation of the tumor suppressor PTEN by SUMO.

The crucial function of the PTEN tumor suppressor in multiple cellular processes suggests that its activity must be tightly controlled. Both, membrane association and a variety of post-translational modifications, such as acetylation, phosphorylation, and mono- and polyubiquitination, have been reported to regulate PTEN activity. Here, we demonstrated that PTEN is also post-translationally modified by the small ubiquitin-like proteins, small ubiquitin-related modifier 1 (SUMO1) and SUMO2. We identified lysine residue 266 and the major monoubiquitination site 289, both located within the C2 domain required for PTEN membrane association, as SUMO acceptors in PTEN. We demonstrated the existence of a crosstalk between PTEN SUMOylation and ubiquitination, with PTEN-SUMO1 showing a reduced capacity to form covalent interactions with monoubiquitin and accumulation of PTEN-SUMO2 conjugates after inhibition of the proteasome. Moreover, we found that virus infection induces PTEN SUMOylation and favors PTEN localization at the cell membrane. Finally, we demonstrated that SUMOylation contributes to the control of virus infection by PTEN.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities

El kéfir es una bebida láctea fermentada. Los gránulo de kéfir, comunidades de microorganismos que se agrupan en una matriz polisacárida denominada kefirano, son los responsables de esta fermentación. Estos gránulos son un ejemplo de simbiosis entre levaduras y bacterias y se han utilizado a través del tiempo para producir el kéfir, que es consumido por todo el mundo a pesar de su origen caucásico. En esa relación simbiótica, que son los gránulos de kéfir, se han aislado e identificado una amplia variedad de especies microbianas que comprenden levaduras y bacterias. El kéfir es un alimento prebiótico. Los prebióticos han demostrado ser beneficiosos para la salud, siendo de gran interés para la industria alimentaria en la actualidad. Según se afirma, el kéfir ha mostrado actividades antibacterianas, antifúngicas y antitumorales, entre otros atributos beneficiosos. Este trabajo incluye una revisión crítica de la composición microbiológica del kéfir junto con sus propiedades beneficiosas para la salud humana(AU)

Kefir is a fermented milk beverage. The milk fermentation is achieved by the of kefir grains, a cluster of microorganisms held together by a polysaccharide matrix named kefiran. Kefir grains are an example of symbiosis between yeast and bacteria. They have been used over years to produce kefir, a fermented beverage that is consumed all over the world, although its origin is Caucasian. A vast variety of different species of organisms forming the kefir grains, comprising yeast and bacteria, have been isolated and identified. Kefir is a probiotic food. Probiotics have shown to be beneficial to health, being presently of great interest to the food industry. Kefir has been accredited with antibacterial, antifungal and antitumoural activities among other beneficial attributes. This review includes a critical revision of the microbiological composition of kefir along with its beneficial properties to human health(AU)